Pressurized Gas Powered Medicament Transfer And Re-Suspension Apparatus And Method

ABSTRACT

Apparatus and method are described employing pressurized gas to transfer, mix and/or reconstitute medicament contained in a vial and flowing it into an injection device. Pressurized gas may be provided by prefilled cartridge.

This application is a divisional of U.S. patent application Ser. No.15/561,820, filed Sep. 26, 2017, currently pending, which is a 371 ofPCT International Application No. PCT/US2016/023973, filed Mar. 24,2016, which claims priority to and the benefit of U.S. ProvisionalApplication No. 62/138,762, filed Mar. 26, 2015, the contents of each ofwhich are hereby incorporated by reference.

The present subject matter relates generally to apparatus and methodsfor transferring and/or mixing medicaments in liquid or un-reconstitutedform in a vial.

BACKGROUND

Drugs, biologics, vaccines, antibiotics and other medical materials(“medicaments”) intended for injection into a subject are commonlysupplied in sealed vials from which the medicament must be withdrawnprior to injection and transferred to an injection device. In some casesthe medicament is in liquid form, and in other cases it is in a dry orpowder form, such as lyophilized form, and must be reconstituted orre-suspended with a liquid diluent before it can be withdrawn from thevial. In this description, “re-suspend” is used in a comprehensive senseto include reconstitute and dilute.

Devices for transferring and/or re-suspending medicaments supplied invials have been the subject of significant development, as haveinjection devices for injecting a medicament into a subject. Examples ofboth are set forth in PCT International Application No.PCT/US2014/042627, entitled Vial Transfer and Injection Apparatus andMethod, which published as PCT Publication No. WO2014204894, on Dec. 24,2014, and is hereby incorporated by reference in its entirety. Variousembodiments of transfer and mixing or re-suspending devices andinjection devices are disclosed in detail therein. The transfer andre-suspending devices shown there employ spring-loaded pistons andcylinders for transferring the medicament and/or diluent and/orre-suspended medicament as between the vial or vials and injectiondevice. While these devices work well, further cost and/or sizereduction and/or simplification continue to be desirable.

SUMMARY

In accordance with one aspect of the present subject matter, pressurizedgas from a source is employed to transfer, mix and/or reconstitutemedicament contained in a vial. The pressurized gas source may be, forexample, a pressure vessel such as but not limited to a pre-filledpressurized gas cartridge or cylinder. More specifically, in one aspect,a method of transferring fluid from a fluid-containing vial to aninjection device is provided. The method may include introducingpressurized gas from a pressure vessel into a vial; flowing fluid fromthe vial under pressure from the gas; and flowing the fluid from thevial into an injection device under the force of the pressurized gas.

In a further aspect, two or more vials may be used and fluid from afirst vial flowed into a second vial to combine or mix with the contentsof the second vial and the combined fluid flowed into an injectiondevice or into one or more additional vials and into an injectiondevice. To reconstitute a lyophilized drug the first vial may contain aliquid diluent and the second vial contain the drug. To dilute a liquidmedicament, the first or second vial may contain a diluent and the othervial contain a liquid medicament. To provide a drug mixture or“cocktail” each vial may contain a liquid medicament. There may be othervariations or combinations, and additional vials employed. The commonfeature is the use of pressurized gas, such as from a pre-filledpressurized gas cylinder or cartridge, to provide energy or force tomove the fluids from vial to vial and into an injection device.

The injection device may include an expandable reservoir, and theresultant fluid, such as combined diluent and medicament or combinedliquid medicaments flowed into the expandable reservoir under pressurefrom the pressurized gas. The pressure may optionally cause thereservoir to expand as it fills with the fluid or the combined diluentand medicament, in effect, charging the injection device for subsequentuse by medical personnel or the subject themselves.

In another aspect of the present disclosure, a medicament transferapparatus is disclosed for transferring fluid from a fluid-containingvial to an injection device including medicament reservoir. Theapparatus includes a pressurized gas source, such as but not limited toa pressure vessel such as a pre-filled pressurized gas cartridge orcylinder, at least one vial receiving station, and a medicationinjection device receiving station. A gas flow path is communicablebetween the gas source and the vial receiving station and a fluid flowpath communicable between the vial receiving station and the medicationinjection device receiving station.

The medicament transfer apparatus may have more than one vial receivingstation and may include, for example, a first vial receiving station anda second vial receiving station, or more. A gas flow path iscommunicable between the pressurized gas source and the first vialreceiving station receiving a vial containing a liquid such as a diluentor liquid medicament. The second and other vial receiving stations maybe configured to receive vials containing any suitable contents, such asa lyophilized drug that is to be reconstituted by a diluent, a liquidmedicament to be diluted by a diluent or mixed with another liquidmedicament or variations of these. A fluid flow path is communicablefrom one vial receiving station to another to allow the desired fluidflow of diluent, medicament or combination. The fluid flow path alsocommunicates between the vials and the injection device receivingstation so that the resultant fluid, whether a reconstituted lyophilizeddrug, diluted medicament or liquid medicament mixture, may be flowedinto an injection device. The motive energy or force for the transfer offluid between the vials and to the injection device receiving station isthe pressurized gas from the pressurized gas source.

The medicament transfer apparatus may also include an injection deviceremovably secured to the device receiving station. The injection devicemay include a reservoir such as one that is expandable under pressure offluid from the force of the pressurized gas.

In accordance with another aspect of this disclosure, anotherre-suspension device is disclosed for re-suspending the medicamentcontents (such as a micro-aggregate) of a vial of the type having anopen end sealed by a septum. This re-suspension device comprises ahousing that includes a diluent port, a gas port, a vent port, and avial receiving station. It also includes a first spike lumen and asecond spike lumen extending from the vial receiving station forpiercing a vial septum when a vial is received at the vial receivingstation. A gas flow path in the housing communicates between the gasentry port and the first spike lumen; a diluent flow path communicatesbetween the diluent port and the first spike lumen; and a vent flow pathcommunicates between the vent port and the second spike lumen. Ahydrophobic filter is cooperatively associated with the vent flow pathfor filtering gas passing the vent flow path and substantiallypreventing the escape of liquid from the vent flow path.

In connection with this aspect, a method of re-suspending medicamentcontents of a vial is also provided. The method comprises: introducingdiluent into the vial; injecting gas under pressure into the vial belowthe level of the diluent in the vial to cause agitation of the diluentand medicament; venting gas from the vial; and continuing the injectingand venting until the medical contents are substantially re-suspended.

BRIEF DESCRIPTION OF DRAWINGS

The above aspects of the present subject matter and many other aspectsare disclosed in following description of the non-exclusive examplesshown in the attached drawings, of which:

FIGS. 1-12 are exemplary views from PCT International Application No.PCT/US2014/042627, entitled Vial Transfer and Injection Apparatus andMethod, which published as PCT Publication No. WO2014204894, on Dec. 24,2014, and are included for background and general disclosure purposes.

Specifically, FIG. 1 is a perspective view of a single-vial systemincluding the single vial holder, transfer apparatus and injectiondevice system embodying the present subject matter.

FIG. 2 is a perspective view of a dual vial system including the dualvial holder, transfer apparatus and injection device system embodyingthe present subject matter.

FIG. 3 includes a perspective view of a single vial holder with theremovable top included, a cross-section of the single vial holder withremovable top included and a perspective view of the single vial holderwith the removable top and vial cap removed.

FIG. 4 includes a perspective view with removable top included and across-section of the dual vial holder with removable top and vial capsremoved.

FIG. 5 is a cross-section of FIG. 2 in the area of the vial holdershowing the position of the vial access members relative to the septumsof the vials.

FIG. 6 is a cross-section of FIG. 1 in the area of the vial holdershowing the vial access member pierced through the septum of the vial.

FIG. 7 is a perspective view of the transfer apparatus shown in FIG. 1showing the vial holder and injection device receiving areas.

FIG. 8 is a close up of FIG. 5 illustrating the vial access memberpiercing the septum of the vial with the collapsible vial access membershield.

FIG. 9 is a schematic of the dual vial transfer system in FIG. 2 with afirst vial, a second vial, a transfer apparatus with a first and secondvariable pressure chambers and injection device including the fluidpathways.

FIG. 10 is a cross-section of FIG. 2 in a pre-fire position.

FIG. 11 is a schematic of the single vial transfer system in FIG. 1 witha drug vial, a transfer apparatus with a first variable pressure chamberand injection device including the fluid pathways.

FIG. 12 is a cross-section of FIG. 1.

FIG. 13 is a flow chart of a method of pressurized gas-powered transferof medicament from a vial to an injection device in accordance with thepresent subject matter.

FIG. 14 is a flow diagram of a method of pressurized gas transfer ofmedicament from a vial to an injection device in accordance with thepresent subject matter.

FIG. 15 is a perspective view of a single vial transfer device embodyingone aspect of the present subject matter.

FIG. 16 is a perspective view of the device of FIG. 15, with a housingportion removed for better view of the interior.

FIG. 17 is a horizontal cross-sectional view of the device of FIG. 15.

FIG. 18 is a perspective view, partially in section, of an alternativesingle vial transfer device embodying an aspect of the present subjectmatter.

FIG. 19 is a perspective view, partially in section, of the device ofFIG. 18 in a different operative position.

FIG. 20 is a flow chart of a method of pressurized gas-powered transferand mixing of contents from two vials and transfer into an injectiondevice in accordance with the present subject matter.

FIG. 21 is a flow diagram of a method of pressurized gas transfer andmixing of contents from two vials and transfer into an injection devicein accorda.

FIG. 22 is a perspective view of a dual vial transfer device embodyingone aspect of the present subject matter.

FIG. 23 is a perspective view of the device of FIG. 22, with a housingportion removed for better view of the interior.

FIG. 24 is a horizontal cross-sectional view of the device of FIG. 22.

FIG. 25 is a cross-sectional view of another system/device useful forthe re-suspension of medicament for injection.

DETAILED DESCRIPTION

FIGS. 1-12 are provided for background and general disclosure purposes.Various functional features shown there may be employed in combinationwith the present subject matter. Referring to FIGS. 1 and 2, as setforth in more detail below, a disposable, one-time use, single vialtransfer and injection system 1 is shown in FIG. 1 and may comprise asingle vial holder 2, transfer apparatus 3 and injection device 7. Adisposable, one-time use, dual vial mixing, transfer and injectionsystem 4 is shown in FIG. 2 and may comprise a dual vial holder 5,transfer apparatus 6 and injection device 7. As mentioned earlier, eachof these aspects has separate utility and may be claimed separatelyand/or in combination or sub-combination.

Referring to FIGS. 3 and 4, the single vial holder 2 shown includes ahousing 8 that includes a side wall 9, end wall 10 and apertures orviewing windows 11. Alternatively the vial holder 2 material may betransparent to allow for visualization of the contents of the vial 12.The housing 8 is shaped to define at least one or two or morevial-receiving cavities (also referred to as stations or zones) 13 forsecurely holding a vial 12 in each zone 13 as shown in FIG. 4. Thecavities 13 in the vial holder 5 may be sized for receiving standardinjectable vial 12 of different sizes such as from 1 to 30 ml. The vial12 may be of the same size or different sizes and may contain anydesired injectable 14.

In the dual vial holder 5 illustrated in FIG. 4, the vials may include,by way of non-limiting example, one vial of powdered, lyophilized orliquid drug 15 and one vial of liquid or diluent 16. There may bevariations and alternatively, for example, each vial may contain liquidmedicament, or one vial contain diluent and the other vial concentratedliquid medicament. The vial holder 5 may have the vials prepackaged andassembled therein by, for example, a drug manufacturer, or the vials maybe inserted into the vial holder 5 by the end user or by a medicalprofessional such as a pharmacist or nurse. The vial holder 5 may haveappropriate markings and/or features to only allow for the assembly ofcertain vials in certain cavities 13. For example, the powdered drugvial 15 may be inserted into a specific cavity 13 of the vial holder 5and diluent vial 16 in another cavity 13 of the vial holder 5. Theapertures or viewing windows 11 in the vial holder 5 allow for directvisualization of the contents 14 of the vials.

Referring to FIGS. 3 and 4, as a further alternative, the vial holder 5may be an assembly of individual vial holders 2, each of which holds asingle vial 12. For example, the injectable manufacturer may preassemblea vial 12 in an individual vial holder 2 which can then be joined withthe vial holder 2 of another vial 12, if needed, at the time ofinjection. For example, a drug manufacturer may provide a lyophilizeddrug 15 in its own vial holder 2 and the diluent 16, such as sterilewater or saline, in a separate vial holder 2. The user or medicalprofessional can then, as needed, join the individual vial holders 2 toform the vial holder assembly 5 for connection to the transfer apparatus6 shown in FIG. 2.

Referring back to FIG. 3, the vial holder 2 may include a removablecover 17 that normally covers and protects the end of the vial 18 duringshipping and storage. Typical standard commercial vials 12 include apierceable septum 19 located in the vial neck for accessing the vialcontents 14, which is covered by a removable vial cap or closure 20. Theremovable cover 17 may be configured to engage the vial cap 20 so thatremoval of the cover simultaneously removes vial cap 20 and exposes thevial septum 19 for accessing the contents 14 after any antisepticswabbing of the septum 19 that may be deemed necessary by the user. Thevial holder 2 may recess the vial 12 therein such that after the vialcap 20 is removed by the cover 17, the pierceable septums 19 arerecessed within the vial holder 2 to reduce the chance of contaminationby the user prior to insertion of the vial holder 2 into the transferapparatus 3 as shown in FIG. 1. This system is applicable to both singlevial holders 2 and dual vial holders 5.

Referring to FIG. 3, the vial holder 2 may include interlocks 27 toprevent the vial 12 from being removed once the vial 12 is inserted intothe vial holder 2. This helps prevent the vial 12 from falling out orbeing inadvertently removed during handling.

Referring to FIG. 5, the vial holder 5 may be assembled to the transferapparatus 6 with the vial caps removed and the vials 15, 16 installedinto the vial holder 5 by the device manufacturer. The exposed vialseptums 19 are held in close proximity to the vial access members 21, 52prior to activation. This configuration provides convenience byeliminating the need for the user to remove the vial caps, swab the vialtops 19 and assemble the vial holder 5 to the transfer apparatus 6 priorto use of the system 4.

Referring to FIG. 6, the vial holder 2 may be packaged separately fromthe transfer apparatus 3. In this case, the user would remove the vialcap with the removable cover 17, swab the vial top 19 (if necessary) andassemble the vial holder 2 into the transfer apparatus 3. As shown inFIG. 6, the vial holder 2 may include lock-out features 22 that interactwith the transfer apparatus 3 to prevent the vial holder 2 from beinginadvertently pulled out of the transfer apparatus 3 after activation bythe user.

Referring to FIG. 5, the vial holder 5 preferably is assembled to thetransfer apparatus 6 to configure the vials 15, 16 upside down in avertical position. This allows any liquid 23 in the vials to be indirect communication with the vial access members 21, 52 after insertionof the vial holder 5. This also forces the air 24 to the top of the vialin this orientation. To encourage the septums 19 to remainuncontaminated after removal of the vial caps and before insertion ofthe vial holder 5, the exposed vial septums 19 may be recessed into thevial holder 5 to prevent inadvertent contact as shown in FIG. 4. Thisconfiguration is applicable to single vial holder and dual vial holderconfigurations.

Referring to FIG. 6, the vial holder 2 preferably is mechanicallyconfigured with insertion features 25 in the transfer apparatus 3 toactuate like an on/off switch, i.e., to only have two states, open andclosed such as a light switch.

This may prevent the user from pushing the vial holder 2 into thetransfer apparatus 3 half way and not allowing the vial access member 21to pierce the septum 19 and allow communication between the contents 14of the vial 12 and the transfer apparatus 3. Additionally, the vialholder 2 may interface with an interlock 26 in the transfer apparatus 3to lock the vial holder 2 in the closed position after full insertion ofthe vial holder 2 to prevent the vial holder 2 from being removed fromthe transfer apparatus 3 after insertion.

Referring to FIG. 7, the transfer apparatus 3 comprises an outer housing28 and defines a vial holder docking area or first receiving station 29and an injection device docking station or second receiving station 30(for removable injection devices). In the illustrated structure, thevial holder docking station 29 and injection device docking station 30are at opposite ends of the transfer apparatus housing 28.

Referring to FIG. 7, the transfer apparatus 3 may have an outer housing28 that is integrated into the packaging 31 of the system. The outerpackaging 31 may essentially form the bottom and side walls of thetransfer apparatus outer housing 28. All of the operational steps inusing the system up to the point of removal of the injection device mayoccur in this packaging 31. This may provide cost reduction and increaseease of use for the user. Additionally, incorporating the entiretransfer apparatus 3 into the packaging 31 eliminates the possible usererror that could occur if the user was required to remove the transferapparatus 3 from the package 31. The packaging 31 could include aplastic tub or tray that contains the system. Furthermore, the packaging31 could include everything within a shipping carton 32 that houses theentire system.

Referring to FIG. 7, the transfer apparatus 3 comprises a vial holderdocking area 29 that may include elongated a vial access member orpiercing member 21. This access member or piercing member 21 could beconfigured as pointed or blunt cannulas or needles. Referring to FIG. 8,the vial holder 5 with attached vial 12 is shown inserted into the vialdocking station 29 and the vial access member 21 piercing the vialseptum 19 allowing access to the contents 14 of the vial 12. The vialaccess member 21 may include a collapsible seal 33 to maintain sterilityof the vial access member 21 and fluid path prior to activation. Thecollapsible seal 33 may also attach and seal on the outside of the vial12 relative to the vial access member 21 to maintain sterility prior toactivation.

Referring to FIG. 8, the vial access member 21 of the transfer apparatus3 may comprise of multi-lumen tubes 34 to communicate with the internalfluid pathways 35 of the transfer apparatus 3. The vial access member 21preferably comprises one inlet tube 36 allowing air or fluid to enterthe vial 12 and one outlet tube 37 allowing for air or fluid to exit thevial 12. These inlet 36 and outlet 37 tubes may be separate and distinctand communicate with different fluid pathways in the transfer apparatus3. Because of the vertical orientation of the vial 12 in the upside-downposition, the lumen openings 38 in the vial access member 21 can beoriented so the inlet tube opening 36 is above the output tube opening37. This orientation allows for introduction of pressurized air orliquid through the upper inlet tube 36 and output of the vial contents14 through the lower output tube 37. Further, the outlet opening 37 maybe positioned near the bottom of the vial 12, adjacent to the septum 19to encourage the entire contents 14 of the vial 12 to enter the outletport 37 and be removed from the vial 12.

Referring to FIGS. 9 and 10, the transfer apparatus 6 is configured tocarry out all of the necessary steps to transfer, mix and/orreconstitute (if necessary) injectable 14 contained within the vials15,16 and transfer the mixture to the injection device 7 preferablyautomatically after user initiation of the process. The transferapparatus 6 is configured and preferably includes a propulsion system orsystems, such as electrically (e.g., battery powered) or mechanically(e.g., spring loaded) actuated pumps, to direct diluent from the diluentvial 16 into the injectable powder vial 15 and to direct the injectable14 through the transfer apparatus 6 into the injection device 7.

Referring to FIGS. 9 and 10, the transfer apparatus 6 may also includean array of internal fluid pathways 35, as required to perform anytransfer, reconstitution, mixing, dilution or other processing of theinjectable 14 and transferring it from the vials 15, 16 in the vialholder 5 to the injection device 7. The fluid pathways 35 may includeflexible or rigid conduits or tubes. These fluid pathways 35 may alsoinclude check valves, filters, flow restrictors or other means 40 todirect the drug from the vials 15, 16 through transfer apparatus 6, intothe injection device 7.

Referring to FIGS. 9 and 10, the transfer apparatus 6 may includevariable volume pressure chambers or cylinders that have movablespring-loaded pistons therein and directly communicate with the internalfluid pathways 35. These chambers would not be required in theembodiment described in the

Summary and in more detail below, which employs a pressurized gas sourceto poser the fluid transfer and/or mixing. In the embodiment of FIGS. 9and 10, the chamber capacity for each variable volume chamber may bedefined by chamber diameter and location of the piston within thechamber. The first pressure chamber 41 in transfer apparatus 6 maypreferably have an initial volume set by the manufacturer in the rangeof 1 to 30 milliliters. The initial contents of the first pressurechamber 41 may preferably include air 45. The piston 43 may be driven bya compression spring 44 in the first pressure chamber 41 whose volume isdefined and set by the manufacturer. The spring-loaded piston 43 may beof adequate size and configuration to produce 1 to 50 psi of static airpressure in the first pressure chamber 41. The volume of air 45 willdepend on the diameter of the chamber 41 and stroke position of thepiston 43 during operation. This pressure will depend on the relativevolume of air 45 displaced by the piston 43 and the force exerted by thespring 44. In other words, the force exerted by the spring 44 multipliedby the area of the piston 43 inside the chamber 4lwill determine thestatic pressure within the chamber 41. The force exerted by the spring44 at its solid height or the beginning of the stroke may be much higherthan the force exerted by the spring 44 at end of its travel. The spring44 may be appropriately sized to control the rate at which air 45 isexpelled out of the pressure chamber 41 and thus the speed of the fluidtransfer in the transfer apparatus 6. The first pressure chamber 41 ispreferably configured to expel all of the air 45 out of the firstpressure chamber 41. Alternatively, a flow restrictor 55 in the outputpath 35 of the pressure chamber 41 could be used to control the rate atwhich air 45 is expelled out of the pressure chamber 41.

Referring to FIGS. 9 and 10, the chamber volume for the second pressurechamber 42 may be set by the manufacturer. Alternatively, the filledchamber volume for the second pressure chamber 42 may be set by the userat time of use using a dose selector or volume controller 48 in therange of 0.5 to 30 milliliters. The spring-loaded piston 46 in thesecond pressure chamber 42 may be of adequate size and configuration toproduce 1 to 200 psi of pressure in the second pressure chamber 42. Adose selector or volume controller 48 permits the user to select aprescribed dosage to be injected by the injection device 7 by settingthe filled volume of chamber 42. The dose selector 48 may be of anysuitable configuration. The dose selector 48 may be directly coupled tothe pressure plunger assembly chamber 93 which is moveable inside thepressure chamber 42. A trigger 49 within the pressure plunger assembly93 releases the piston 46 in the second pressure chamber 42 once thepiston has reached a position corresponding to the filled volumesetting. The user selects the desired dosage positions in the secondpressure chamber 42 by moving the dose selector 48 which positions thepressure chamber plunger assembly 93 to define a filled chamber volumeequal to the desired injection dosage. Alternatively, the position ofthe pressure plunger assembly 93 may already be set by the manufacturecorresponding to the delivery dose and the user operates the devicewithout making a dose adjustment.

Referring to FIGS. 9 and 10, the transfer apparatus 6 for a dual vialsystem 4 that provides for mixing and transfer includes a vial holder 5with a first vial 16 and second vial 15, a first variable volumepressure chamber 41, a second variable volume dose pressure chamber 42,fluid pathways 35, and check valves 40 to direct air from the firstpressure chamber 41 into the first vial 16 and the contents 23 of thefirst vial 16 into the second vial 15 and the resulting mixture 14 inthe second vial 15 into the second pressure chamber 42 which is thentransferred into the injection device 7.

Referring to FIG. 8, upon complete insertion of the vial holder 5 intothe transfer apparatus 6 and the subsequent introduction of the vialaccess members 21 through the septums 19 and into the vial chambers 12by the user allows for the release of the pressure chamber trigger 50shown in FIG. 10.

Referring to FIGS. 9 and 10, release of the trigger 50 then releases thefirst pressure chamber spring 44 allowing the advance of the firstpressure chamber piston 43 in the first pressure chamber 41 causing theair 45 in the first pressure chamber 41 to be forced through the inlettube 36 of the first vial access member 21 and into the first vial 16through internal passage ways 35 in the transfer apparatus 6. As moreair 45 is forced out of the first pressure chamber 41 and into the firstvial 16 through the inlet tube 36, the air 45 rises to the top of thefirst vial 16 due to its vertical orientation within the vial holder 5.The increasing air pressure in the first vial 16 causes the fluid 23 inthe vial 16 to be expelled through the outlet tube 37 of the first vialaccess member 21 and through the inlet tube 51 of the second vial accessmember 52. The fluid 23 from the first vial 16 entering the second vial15 mixes with the contents 54 of the second vial 15 containing theliquid or powdered medicament and exits though the outlet tube 53 of thesecond vial access member 52 and into the second pressure chamber 42. Inthe same manner within the reconstitution configuration, the advancingplunger 43 in the first pressure chamber 41 continues to push a firstfluid 23 then air 45 mixture through the first vial 16 into the secondvial 15. The increasing air pressure in the top of the second vial 15causes the reconstituted or other mixture 14 in the bottom of the secondvial 15 to be expelled out into the second pressure chamber 42. A‘popoff’ or check valve 40 or other type of valve may be present on theoutlet tube 53 of the second vial access member 52 to encourage all ofthe contents 23 of the first vial 16 to enter the second vial 15 beforethe contents 14 of the second vial 15 are expelled out into the secondpressure chamber 42. The valve would not open until the pressurecorresponding to the plunger 43 pushing substantially all the air 45 outof the first pressure chamber 41. This ensures that the contents 54 ofthe second vial 15 may be thoroughly mixed with the contents 23 of thefirst vial 16 before the mixture 14 exits the second vial 15 and intothe second pressure chamber 42. Alternatively, a flow restrictor 55 maybe used in the fluid pathway 35 to delay the transfer and increase themixing time.

Referring to FIGS. 9 and 10, injectable drug 14 flows from the secondvial 15 after mixing, diluting and/or reconstitution, into the secondpressure chamber 42, filling the chamber 42 to the extent permitted bythe piston 46 position as selected using the dose indicator 48 by theuser or manufacturer, which corresponds to the desired dosage. When thedesired volume of the second pressure chamber 42 has been achieved, thesecond pressure chamber trigger 49 releases the spring 47 and forces thepiston 46 forward, expelling the selected dosage of injectable drug 14under pressure into the injection device 7. Calibration of the dosevolume shown on the dose selector 48 and the actual dose received by theuser may be required to account for fluid loss in the internal pathways35 of the transfer apparatus 6. The injection device 7 is now full andready to remove from the transfer apparatus 6.

Referring to FIGS. 11 and 12, an alternative transfer apparatus 3 withina single vial system 1 that does not perform mixing but only transfersfluid 14 from a single vial 15 to the injection device 7 is provided.This alternative transfer apparatus 3 includes a vial holder 2 withsingle vial 15, a variable volume pressure chamber 56, fluid pathways35, and check valves 40 to direct the contents 14 from the vial 15 intothe injection device 7. The inlet tube 36 of the vial access member 21is vented to the environment 57 to allow air 58 to enter the vial 1. Theoutlet tube 37 of the vial access member 21 is connected to the pressurechamber 56.

Referring to FIGS. 11 and 12, the full insertion of the vial holder 2into the transfer apparatus 3 by the user causes the introduction of thevial access member 21 through the septum 19 of the vial 15 to access thecontents 14 of the vial 15. This also triggers the release of thepressure chamber trigger 59. The pressure release trigger 59 releasesthe plunger 60 within the pressure chamber 56 connected to a withdrawspring 61. The withdraw spring 61 forces the plunger 60 to retract andwithdraw fluid 14 from the vial 15 and fill the pressure chamber 56. Aspecified amount of fluid 14 withdrawn by the chamber 56 could be set bythe manufacturer by limiting the retraction of the plunger 60.Additionally, the chamber 56 can be configured to withdraw all of thefluid 14 from the vial 15 by retracting the plunger 60 to its fulltravel. Once the plunger 60 reaches a set position within the pressurechamber 56, it interacts with a dispense trigger 62 that releases adispense spring 63 to force the liquid 14 out of the pressure chamber 56into the injection device 7. Check valves 40 could be employed toprevent fluid 14 from going back into the vial 15.

Pressurized Gas-Powered Transfer and/or Mixing

In accordance with the present subject matter shown in FIGS. 13-24, thetransfer and/or mixing and re-suspension are powered by a pressurizedair source, such as a pressure vessel, which may be in the form ofpre-filled pressure cylinder or cartridge. This allows for theelimination of the variable volume pressure chambers or cylinders thathave movable spring-loaded pistons as described above and providespotential reduction in cost and size for the transfer andmixing/re-suspending apparatus.

Turning now to FIG. 13, this flow chart provides an overview of a singlevial fluid transfer method and generally depicts some exemplary steps inusing a pressurized gas source to power the transfer. The structures andmore specific aspects of the structures for carrying out the process ormethod will be described later.

Every step in FIG. 13 may not be required in all embodiments. Asreflected in the flow chart, a vial containing liquid medicament isinserted into a vial receiving station of the transfer device, which mayhave a spike for piercing the vial septum and accessing the contents.The spike may have two lumen, one for entering gas and another foroutflow of medicament, or two separate spikes may be used.

The method is initiated by the user by actuating a gas triggeringmechanism which may be of various different configurations. As explainedlater, the triggering mechanism may be actuated upon insertion of thevial into the vial receiving station or thereafter. For example, theinsertion may release a spring force that forces a piercing orpuncturing pin through a sealing diaphragm or cap associated with apre-filled pressure cylinder or cartridge. Alternatively, the user's ownforce when inserting the vial into the receiving station may be employedto force together a pre-filled gas cylinder and piercing pin to accessthe pressurized gas. These are only a couple of non-limiting examples.

The pre-filled pressurized gas cartridge or cylinder may contain gasunder very high pressures, such as 500 psig or more, for example 900psig or greater, and even up to 2,000-3,000 psig or more. Accordingly,it may be desired to direct the pressurized gas flowing from thepressure cylinder or cartridge through a flow restrictor, such as asmall orifice, and/or a pressure regulator to control the gas flow rateand/or gas pressure before it enters the vial.

The pressurized gas is directed into the vial, and the pressure of thegas forces liquid medicament from the vial and into an injection device.A feedback mechanism may be provided to indicate when the contents ofthe vial have been fully transferred to the injection device, and a ventmay exhaust surplus gas to the ambient atmosphere. Because the volume ofthe pre-filled cylinder is small, such as 5 ml or less, or even 2 ml orless, the gas vented into the atmosphere will be relatively de minimusand may not even be noticeable to the user.

After transfer to the injection device is completed, the injectiondevice may be removed from the transfer device and used in the mannerpreviously described in the earlier identified PCT publicationWO2014/204894.

FIG. 14 is a diagrammatic view of the single vial transfer system,including a pressure vessel in the form of a prefilled pressurized gascylinder or cartridge 100, a flow restrictor and/or pressure regulator101, a liquid medicament vial 102 and an injection device 103. The gascylinder may be any suitable cylinder commercially available or may be acustom cylinder. For example, a variety of potential cylinders areavailable from Leland Gas Technologies of South Plainfield, N.J., USA,which manufactures high pressure gas filled disposable cylinders incapacities from 1 to 1000 cc. The cylinders may be charged to suitablepressures up to 2000-3000 psig or more. It is understand that relativelysmall capacity disposable cylinders will be suitable for the presentsubject matter. For example, the cylinder may have a volume of 10 ml orless, and more preferably less than 5 ml, such as 1-2 ml, pressurized to500 psig or more, such as from 900 psig up to 2000-3000 psig or more.

The gas may be any suitable gas, such as, but not exclusively, an inertgas. As it will come in contact with medicament, the gas is preferablypathogen free—i.e., free of active pathogens. Nitrogen or argon may besuitable gases. When released from the cylinder, such as by puncture bya piercing pin, the gas is directed through a suitable flowpath from thecylinder through the flow restrictor and/or pressure regulator 101 tothe vial 102.

The flow restrictor and/or pressure regulator 101 may be of any suitableconfiguration, preferably small and disposable. A typical flowrestrictor may be a diaphragm with a small orifice to limit the flowrate of gas from the cylinder. If desired a pressure regulator may alsobe included in combination with or separate from the restrictor. Fromthe restrictor/regulator, flow path 104 conducts the gas to the vial102.

The vial 102 may be a standard drug vial with a rigid container portion105 usually glass, open at one end and sealed by a piercable diaphragmor septum 106 of latex, silicone or other material. The present processis preferably carrried out with the vial in inverted vertical positionso that the gas flows to the closed end of the vial, forcing essentiallyall the medicament from the vial under the force of the pressurized gas.

From the vial, flow path 107 directs the medicament under the pressureof the gas to a suitable vessel such as an injection device 103. Theinjection device has a medicament reservoir, such as an expandablereservoir for receiving the medicament, for example a reservoir thatexpands under pressure from the medicament. The reservoir may be biasedto expel the medicament upon user actuation of the injection device. Inthe illustrated embodiment, the injection device 103 has an elastomericexpandable bladder that is initially empty and expands as it is filledwith medicament flowed thereinto under the force or pressure of the gasfrom cylinder 100. The elastomeric quality of the bladder biases it toexpel the medicament into the subject when later activated by the user,as described in the previously filed PCT application identified above.

FIG. 15 illustrates one potential transfer device, generally at 108, foreffecting the transfer of liquid medicament from a vial 102 to aninjection device 103 as generally described above. The illustratedtransfer device has a rigid plastic housing 109 that includes a vialreceiving station 110, shown with vial 102 inserted, and an injectiondevice receiving station 111, shown with the injection device 103 inplace. The housing 109 contains the fluid flow paths and variousoperative mechanisms for effecting the transfer of medicament to theinjection device from the vial.

This may be better seen in FIG. 16, which is similar to FIG. 15 but withthe upper part of the housing 109 removed to allow viewing of certain ofthe inner parts. The fluid flow paths, which may be of any suitableconfiguration, such as plastic tubing, are not visible in FIG. 16. Withthe removal of the upper part of the housing in FIG. 16, the gascylinder or cartridge 100 may be seen in the pre-fill or pre-fireposition, before the gas is released by a piercing pin 112. In thepre-fill position, the cylinder is positioned between a compressedspring, generally shown as member 113, and a pivotable or slidable latchor lever 114 that blocks movement of the gas cylinder toward thepiercing pin. Insertion of the vial 102 into the vial receiving stationsimultaneously forces one or more access spikes (not seen in FIG. 16)through the vial septum 106 and depresses latch 114. When latch 114 isdepressed, it releases the pressurized gas cylinder 100 for movementagainst the piercing pin 112 under the force of compressed coil spring113. This causes the pin to pierce a puncture area or sealing cap on thepressure cylinder and allows the compressed gas to flow from thecylinder through the pin. Although described with the spring 113 forcingthe cylinder 100 against the pin 112, alternatively the pin could bemoved against the cylinder. Also, other types of force-generatingdevices other than a coil spring could be utilized.

FIG. 17 is a top view of the lower portion of housing 109, with the vial102 and injection device 103 removed to better illustrate the respectivepositions of the pressure cylinder 100, compressed spring 113 and latch114. The position shown is with the latch blocking movement of thecylinder and prior to puncture of the pressurized gas cylinder by thepiercing pin 112.

FIG. 18 shows one possible alternative transfer device with a differentarrangement for insertion of the vial 102 to cause puncture of thepressure cylinder 100. The transfer device 115 includes a housing 116with a vial receiving station 117 and an injection device receivingstation 118 with the vial 102 and injection device 103 shown in theirrespective stations. In this embodiment, the vial 102 has an outer shellor jacket 119 that is threaded at one end 120 and includes a radialouter flange 121. The vial receiving station 117 of the transfer deviceis internally threaded to receive the threaded end of the vial jacket119. Insertion and rotation of the vial jacket 119 forces an accessspike 122 through the septum 106 of the vial. Continued rotation of thevial jacket causes the radial flange 121 to engage against a pushingmember 123 located against the closed end of the pressurized gascylinder 100. With additional rotation of the vial jacket, as best seenin FIG. 19, the pushing member 123 pushes the cylinder against piercingpin 124, causing it to pierce the seal cap of the cylinder and allowinggas to flow from the cylinder through flow passageways, not shown,through the access spike122 (or a separate access spike) and into thevial 102 to force liquid medicament from the vial and into the injectiondevice 103. The threaded connection between the transfer devicereceiving station and the vial jacket affords a mechanical advantage tothe puncturing of the vial and the cylinder that may be beneficial topatients who have limited strength or dexterity.

As shown in FIGS. 18 and 19 there is a single access spike 122. In thatsituation, the spike will typically include two lumen or flow paths. Onelumen will be for entry of gas and the other for outflow of liquidmedicament. The outflow lumen may open in proximity to the insidesurface of the septum, or at the lowest practical location when the vialis inverted, so that it is below the surface of the medicament and at alocation so as to drain essentially all of valuable medicament from thevial. The gas entry lumen may open into the vial near the distal end ofthe spike 140, and spaced a substantial distance from the outflow lumen,so that substantially all the medicament flows from the vial before gasexits. The gas lumen may be configured open above the level of themedicament (when the vial is inverted) to enhance liquid transfer andreduce the risk of gas entrainment in the liquid. Alternatively, the gasinflow and liquid outflow lumen could be contained in separate spikes,particularly where the vial is pushed into the receiving station. In thethreaded version of FIGS. 18 and 19, a single spike, with two lumen,would normally be used.

Turning now to FIG. 20. FIG. 20 is as flow chart, similar to FIG. 13,but in this case providing an overview of a dual vial fluid transfermethod and some exemplary steps of the method using a pressurized gassource to power the transfer of contents, such as for example, diluentfrom a diluent vial into a medicament vial and combined diluent andmedicament from the medicament vial, into an injection device.Alternatively, as noted earlier, a pressurized gas source may be used topower the transfer of medicament from a first liquid medicament vialinto a second liquid medicament vial and the combined medicaments fromthe second vial into an injection device. Or, one of the vials maycontain a diluent and the other vial contain concentrated liquidmedicament. Other variations may also be employed.

Every step in FIG. 20 may not be required in all embodiments. Asreflected in the flow chart, a vial containing medicament and a vialcontaining diluent are inserted into a vial receiving station of atransfer device, with a separate spike for piercing the vial septum andaccessing the contents of each vial. Each spike may have two lumen, onefor entering gas and another for outflow of diluent or medicament, ortwo separate spikes may be used for each vial.

The method is initiated by the user, as in the single vial process, byactuating a gas triggering mechanism which may be of various differentconfigurations. As explained, the triggering mechanism may be actuatedupon insertion of a vial into the vial receiving station or thereafter.Similar to the single vial system explained above, vial insertion mayrelease a spring force that forces a piercing or puncturing pin througha sealing diaphragm or cap associated with a pre-filled pressurecylinder or cartridge-either by moving the puncturing pin or thepressure cylinder or both. Alternatively, the user's own force wheninserting the vial into the receiving station may be employed to force apre-filled gas cylinder and piercing pin together to access thepressurized gas. These are only a couple of non-limiting examples.

The pre-filled pressurized gas cartridge or cylinder, the gas itself,the flow restrictor and/or pressure regulator are generally as describedabove in connection with FIG. 13, although the pressurized gas cylinderused in a dual vial system may need to be of larger capacity and/orhigher pressure than in the single vial system.

In the dual vial system, the pressurized gas is typically first directedinto the first vial, such as a liquid medicament or a diluent-containingvial, and the pressure of the gas forces the liquid medicament ordiluent from the first vial into a second or medicament vial. As notedin the introduction, the medicament may be a powder or in lyophilizedform, and injection of the diluent is required to re-suspend orreconstitute the medicament. Both vials could also contain liquidmedicaments or diluent and liquid medicament. The force of thepressurized gas also forces the resulting fluid, such as re-suspendedmedicament, from the second or medicament vial and into the injectiondevice. A feedback mechanism may be provided to indicate when thecontents of the medicament vial have been fully transferred to theinjection device, and a vent may exhaust surplus gas to the ambientatmosphere. Because the volume of the pre-filled cylinder is small, theventing gas into the atmosphere will be relatively de minimus and maynot even be noticeable to the user. As noted above, each vial couldcontain a liquid medicament, with a mixture or “cocktail” of the twomedicaments, e.g., drugs, forced into the injection device.

After transfer to the injection device is completed, the injectiondevice may be removed from the transfer device and used in the mannerpreviously described in the published PCT application identified above.

For purposes of illustration and not limitation, FIG. 21 is adiagrammatic view of a pressurized gas powered dual vial re-suspensionand transfer system, including a pressure vessel in the form of aprefilled pressurized gas cylinder or cartridge 200, a flow restrictorand/or pressure regulator 201, a liquid diluent vial 202D, a medicamentvial 202M and an injection device 203. (Each vial 202D and 202M couldalso contain liquid medicament). The gas cylinder may be any suitablecylinder commercially available or may be a custom cylinder, aspreviously explained in connection with the single vial system.

Also similar to the single vial system, the gas may be any suitable gas,such as, but not exclusively, an inert gas preferably pathogenfree—i.e., free of active pathogens. When released, such as by punctureby a piercing pin, the gas is directed through a suitable flowpath fromthe cylinder through the flow restrictor and/or pressure regulator 201into the diluent vial 202D.

The flow restrictor and/or pressure regulator 201 may be of any suitabledesign, preferably small and disposable. A typical flow restrictor maybe a diaphragm with a small orifice to limit the flow rate of gas fromthe cylinder. If desired, a pressure regulator may also be included incombination with or separate from the restrictor. From therestrictor/regulator, the flow path 204 conducts the gas to the diluentvial 202D.

The diluent (or first liquid medicament) vial 202D and medicament (orsecond liquid medicament) vial 202M may each be of standard drug vialconfiguration with a rigid container portion 205 usually glass, open atone end and sealed by a piercable diaphragm or septum 206 of latex,silicone or other material. The present process is preferably carriedout with the vials in inverted vertical position so that the gas flowsto the closed end of the vials, forcing essentially all the diluentand/or medicament from the vials under the force of the pressurized gas,before any gas exits the medicament vial.

From the diluent (or first liquid medicament) vial 202D, flow path 207Ddirects the diluent (or liquid medicament) under the pressure of the gasinto the medicament vial 202M, where it may re-suspend the medicament ifin a dry of lyophilized form or dilute the medicament if in liquidconcentrated form (or simply combine or mix with the medicament if inliquid non-concentrated form). From the medicament vial 202M, combinedmedicament and diluent or diluted or mixed liquid medicament flowsthrough flow path 207M under the pressure of the gas to any suitablevessel, such as an injection device 203 as disclosed in the previouslyidentified PCT application. As pointed out above, the injection devicemay have an expandable reservoir, such as an elastomeric bladder, forreceiving the medicament.

FIG. 22 illustrates one potential transfer device, generally at 208, foreffecting the transfer of liquid diluent or medicament from vial 202D tomedicament vial 202M and from the medicament vial 202M into an injectiondevice 203. The illustrated transfer device has a rigid plastic housing209 that includes a dual vial receiving station 210, shown with vials202D and 202M inserted, and an injection device receiving station 211,shown with the injection device 203 in place. The housing contains thefluid flow paths and operative mechanisms for effecting the transfer ofdiluent or medicament and resultant medicament to the injection devicefrom the vials.

This may be better seen in FIG. 23, which is similar to FIG. 22, butwith the upper part of the housing 209 removed to allow view of certainof the inner parts. The fluid flow paths, which may be of suitableconfiguration, such as plastic tubing, are not visible in FIG. 23. Withthe removal of part of the housing in FIG. 23, the gas cylinder orcartridge 200 may be seen in a position before the gas is released by apiercing pin 212. In this position, the cylinder is positioned between acompressed spring, generally seen as member 213, and the pivotable orslidable latch or lever 214 which normally blocks movement of the gascylinder toward the piercing pin.

Insertion of the vial pair 202D and 202M into the vial receiving station210 simultaneously forces one or more access spikes (not seen in FIG.23) through the vial septum of each vial and depresses the latch 214.When latch 214 is depressed, it moves to a non-blocking position,releasing the pressurized gas cylinder 200 for movement against thepiercing pin 212 under the force of compressed coil spring 213, causingthe pin to pierce a puncture area or sealing cap on the pressurecylinder and allowing the compressed gas to flow from the cylinder.Although described with the spring forcing the cylinder against thespike, alternatively the spike could be moved against the cylinder, andother types of force-generating devices other than coil springs could beutilized. If desired, both the spike and cyclinder could be moved towardone another by the same or different force-generating devices.

FIG. 24 is a top view of the lower portion of housing 214, with thevials 202D and 202M and injection device 203 removed to betterillustrate the respective positions of the pressure cylinder 200, spring213 and latch 214. The position shown is with the latch blockingmovement of the cylinder and prior to puncture of the pressurized gascylinder by the piercing pin 212.

FIG. 25 is a cross-sectional view of a system 230 for re-suspending adry or micro-aggregate material stored in a container such as vial 231.The components of the system shown in FIG. 25 are exemplary only and maybe varied as will be apparent after reading this description. In theillustrated embodiment, the system includes a housing, generally at 232that has a vial receiving station 233, a diluent receiving port 234, agas connection port 235 and vent port 226.

The illustrated vial receiving station 233 has two piercing spikes 227and 228 for penetrating the septum of vial 231. Spike 227 extendssubstantially into the vial so as to open near the bottom of the vialand spaced from the vial septum, when it is inverted in a verticalposition. Spike 228 is shorter and opens into the vial at a location inproximity to the inside surface of the septum. Each spike has a lumen.The lumen of spike 227 communicates, via tubing or other flow path inthe housing 232, with the vent port 226. The lumen of spike 228communicates with a flow path 229 that extends between the spike and oneport on 3-way valve 230. Flow path 231 extends between another port onthe 3-way valve and the diluent port 234, and flow path 232 extendsbetween a third port on the three-way valve and gas port 235.Alternatively, a single piercing spike with dual lumen could also beused.

In the illustrated system, a syringe 233 is attached to the diluent port234. The syringe can provide a source of diluent for re-suspension ofthe micro-aggregate in the vial and a means for later withdrawal of thesuspension from the vial. In addition, a filter 234 is attached to thevent port 226. The filter may take any suitable form and is preferablyhydrophobic to prevent liquid from escaping into the environment, aswill be described below.

In operation, the vial 231 containing a dry material such as amedicament in micro-aggregate form is first attached to the vialreceiving station 233. A diluent containing syringe 233 is attached tothe diluent port 234, and a pressurized gas source (not shown) isattached to gas port 235. The three-way valve is set for the diluent toflow from flow path 231 into the fluid flow path 229 leading to spike228. The diluent is injected from the syringe into the vial. The valve230 is then turned so that gas can flow from the gas port 235, throughpassageway 229 into the spike 228. The spike 228 opens into the vialbelow the level of the diluent and the bubbling gas entering the vialcauses agitation between the diluent and micro-aggregate material. Thegas rises to the bottom of the inverted vial and exits through the lumenof spike 227. In the event that the gas carries any liquid with it, thehydrophobic filter 234 in the vent flow path prevents the escape of theliquid while allowing the gas to continue to vent.

The introduction of gas into the vial continues for a selected period oftime until the micro-aggregate is substantially fully suspended in thediluent due to the agitation of the entering gas. The 3-way valve isthen returned to the position where the diluent flow path 231 and flowpath 229 are in communication, and the syringe 233 is retracted towithdraw the suspended micro-aggregate from the vial. The filter 234allows displacement air to vent into the vial, and the position of spike228 allows substantially all of the micro-aggregate to be withdrawn fromthe vial. With this system, the micro-aggregate can be reliably andpredictably re-suspended without concern for the uncertainty andvariability that can occur when manual re-suspension is employed.

Additional Aspects and Variations

Without limiting any of the foregoing or the attached claims, othergeneral and more specific aspects and variations of the subject matterof this description are set forth below.

Aspect 1 is a method of transferring fluid from a fluid-containing vialto an injection device comprising: introducing pressurized gas into avial; flowing fluid from the vial under pressure from the gas; andflowing the fluid from the vial into an injection device under the forceof the pressurized gas.

Aspect 2 is the method of aspect 1 in which the fluid is a diluent andthe pressurized gas is flowed into the diluent-containing vial anddiluent is flowed from the diluent-containing vial into amedicament-containing vial and combined diluent and medicament is flowedfrom the medicament-containing vial into the injection device underpressure from the pressurized gas.

Aspect 3 is the method of aspect 1 in which the vial is a first vialcontaining a first liquid medicament and the first medicament is flowedfrom the first vial into a second vial containing a second liquidmedicament, and mixed first and second medicaments are flowed from thesecond vial into an injection device under the force of the pressurizedgas.

Aspect 4 is the method of aspect 1, 2 or 3 in which the injection deviceincludes an expandable reservoir, and the fluid or the combined diluentand medicament or the mixed first and second medicaments is flowed intothe expandable reservoir under pressure from the pressurized gas.

Aspect 5 is the method of aspect 3 in which the expandable reservoircomprises an elastomeric bladder.

Aspect 6 is the method of aspect 3 or 4 in which the reservoir is biasedto expel the fluid or combined diluent and medicament or mixed first andsecond medicaments.

Aspect 7 is the method of any one of aspects 1-6 in which thepressurized gas is flowed from a pre-filled pressure vessel.

Aspect 8 is the method of aspect 7 in which the vessel includes apuncturable seal and the method includes puncturing the seal.

Aspect 9 is the method of any one of aspects 1-8 in which the gas isessentially pathogen free.

Aspect 10 is the method of any one aspects 1-9 including filtering thegas before it enters a vial.

Aspect 11 is the method of any one of aspects 7-10 in which the pressurevessel is a gas-filled cartridge having a volume of 10 ml or less.

Aspect 12 is the method of aspect 11 in which the cartridge has volumeof about 1 ml or less.

Aspect 13 is the method of any one of aspects 7-12 in which the pressurevessel initially contains gas at a pressure of greater than about 500psig.

Aspect 14 is the method of any one of aspects 1-13 in which the gas isan inert gas.

Aspect 15 is the method of any one of aspects 1-14 in which the gas isselected from the group consisting of nitrogen, helium, neon, argon,krypton, and xenon.

Aspect 16 is the method of any one of aspects 4-16 including removingentrained gas from the fluid before it enters the expandable reservoir.

Aspect 17 is the method of any one of aspects 1-16 in which thepressurized gas is flowed from a pre-filled cartridge having a volume ofabout 1 ml or less and a pressure of about 900 psig or greater.

Aspect 18 is the method of any one of aspects 1-17 including controllingthe flow rate and/or pressure of gas.

Aspect 19 is medicament transfer apparatus for transferring fluid from afluid-containing vial to an injection device, comprising a pressurizedgas source, at least one vial receiving station, and a medicationinjection device receiving station, a gas flow path communicable betweenthe gas source and the vial receiving station and a fluid flow pathcommunicable between the vial receiving station and the medicationinjection device receiving station.

Aspect 20 is the medicament transfer apparatus of aspect 19 in whichtransfer apparatus includes at least a first vial receiving station anda second vial receiving station and the gas flow path is communicablebetween the pressurized gas source and the first vial receiving stationand the fluid flow path is communicable between the first vial receivingstation and the second vial receiving station and between the secondvial or final receiving station and the injection device.

Aspect 21 is the medicament transfer apparatus of aspect 19 or 20 inwhich the pressurized gas source comprises a pre-filled pressure vessel.

Aspect 22 is the medicament transfer apparatus of aspect 21 in which thevessel includes a puncturable seal and the apparatus includes apuncturing pin for puncturing the seal.

Aspect 23 is the medicament transfer apparatus of aspect 21 including anactuator for moving the puncturing pin and/or the pressure vesselbetween a pre-puncture position and a puncture position.

Aspect 24 is the medicament transfer apparatus of aspect 22 in which theactuator comprises a stored energy source biased to move the puncturingpin and/or the pressure vessel to the puncture position.

Aspect 25 is the medicament transfer apparatus of aspect 23 in which thestored energy device comprises a spring.

Aspect 26 is the medicament transfer apparatus of aspect 21 in which thepuncturing pin includes a seal for contacting the pressure vessel tolimit the escape of pressurized gas into the ambient environment.

Aspect 27 is the medicament transfer apparatus of any one of aspects19-26 in which the pressurized gas is essentially pathogen free.

Aspect 28 is the medicament transfer apparatus of any one of aspects19-27 in which the gas flow path includes a filter for filtering the gasbefore it enters a vial.

Aspect 29 is the medicament transfer apparatus of any one of aspects19-28 in which the pressurized gas source is a pre-filled gas cartridgehaving a volume of 10 ml or less.

Aspect 30 is the medicament transfer apparatus of any one of aspects19-29 in which the pressurized gas source has volume of about 1 ml orless.

Aspect 31 is the medicament transfer apparatus of any one of aspects19-30 in which the pressure source initially contains gas at a pressuregreater than about 500 psig.

Aspect 32 is the medicament transfer apparatus of any one of aspects19-31 in which the gas is an inert gas.

Aspect 33 is the medicament transfer apparatus of any one of aspects19-31 in which the gas is selected from the group consisting ofnitrogen, helium, neon, argon, krypton, and xenon.

Aspect 34 is the medicament transfer apparatus of any one of aspects19-32 in which the fluid flow path includes a gas trap for removingentrained gas from the fluid before it enters the injection device.

Aspect 35 is the medicament transfer apparatus of any one of aspects19-32 in which the pressurized gas source is a pre-filled cartridgehaving a volume of about 1 ml or less and a pressure of about 900 psigor greater.

Aspect 36 is the medicament transfer apparatus of any one of aspects19-35 including a flow regulator and/or pressure regulator forcontrolling the flow rate and/or pressure of gas from the pressurizedgas source.

Aspect 37 is the medicament transfer apparatus of any one of aspects19-36 including a medicament injection device received in the injectiondevice receiving station.

Aspect 38 is the medicament transfer apparatus of aspect 37 in which theinjection device includes a reservoir that is expandable under pressureof fluid or combined diluent and medicament or mixed medicament flowunder the force of pressurized gas.

Aspect 39 is the medicament transfer apparatus of aspect 38 in which theexpandable reservoir comprises an elastomeric bladder.

Aspect 40 is the medicament transfer apparatus of aspect 38 or 39 inwhich the expandable reservoir is biased when expanded to expel thefluid or combined diluent and medicament or mixed medicament.

Aspect 41 is a re-suspension device for re-suspending medicamentcontents of a vial of the type having an open end sealed by a septum,the re-suspension device comprising: a housing including; a diluentport; a gas port; a vent port; a vial receiving station; a first spikelumen and a second spike lumen extending from the vial receiving stationfor piercing a vial septum when a vial is received at the vial receivingstation; a gas flow path communicating between the gas entry port andthe first spike lumen; a diluent flow path communicating between thediluent port and the first spike lumen; a vent flow path communicatingbetween the vent port and the second spike lumen; and a hydrophobicfilter cooperatively associated with the vent flow path for filteringgas passing the vent flow path and substantially preventing the escapeof liquid from the vent flow path.

Aspect 42 is the re-suspension device of aspect 41 comprising a flowjunction between the gas flow path and the diluent flow path upstream ofthe first spike lumen and a valve associated with the flow junction tocontrol flow of gas and/or diluent, respectively, between the firstspike lumen and the gas port and the first spike lumen and the diluentport.

Aspect 43 is the re-suspension device of aspect 41 or 42 in which thefirst spike lumen and second spike lumen are defined in a singlepiercing spike.

Aspect 44 is the re-suspension device of aspect 41 in which the firstspike lumen is defined in a first piercing spike and the second spikelumen is defined in a separate second piercing spike.

Aspect 45 is the re-suspension device any one of aspects 41-44 in whichthe second spike lumen has a greater length than the first spike lumenso as to extend farther into a vial received at the receiving station.

Aspect 46 is the re-suspension device of any one of aspects 41-45 inwhich the first spike lumen is configured to open into a vial so as tobe below the level of diluent during re-suspension and the second spikelumen is configured to open into the vial at a location so as to beabove the level of diluent during re-suspension.

Aspect 47 is the re-suspension device of any one of aspects 41-46 inwhich the first spike lumen is configured to open into a vial at alocation proximal to the septum and the second spike lumen is configuredto open into the vial at a location substantially spaced from theseptum.

Aspect 48 is a method of re-suspending medicament contents of a vial,the method comprising: introducing diluent into the vial; injecting gasunder pressure into the vial below the level of the diluent in the vialto cause agitation of the diluent; venting gas from the vial; andcontinuing the injecting and venting until the medical contents aresubstantially resuspended.

Aspect 49 is the method of re-suspending of aspect 48 includingsubstantially preventing the escape of liquid with the venting gas.

Aspect 50 is the method of re-suspending of aspect 48 or 49 in which theventing gas is passed through a hydrophobic filter to substantiallyprevent the escape of liquid from the vial.

Aspect 51 is the method of any one of aspects 48-50 in which gas isvented from the vial at a level above the level of diluent.

Aspect 52 is the method of any one of aspects 48-51 in which themedicament contents of the vial are substantially in a dry state.

Aspect 53 is the method of any one of aspects 48-52 in which themedicament contents of the vial comprise a lyophilized material.

Aspect 54 is the method of any one of aspects 48-53 in which the gas issubstantially free of pathogens.

Although the present subject matter has been described with reference tothe illustrated examples and various aspects and variations, this isonly purposes of explanation and not limitation. It is understood thatthe present subject matter may have application in other circumstancesor may be varied in detail without departing from the disclosure herein.

1. A method of transferring fluid from a fluid-containing vial to aninjection device comprising: introducing pressurized gas into a vial;flowing fluid from the vial under pressure from the gas; flowing thefluid from the vial into an injection device under the force of thepressurized gas.
 2. The method of claim 1 including combining amedicament with the fluid after flowing the fluid from the vial andbefore flowing the fluid into an injection device.
 3. The method ofclaim 2 in which the combining step includes flowing the fluid from thevial under pressure from the gas into a second vial containingmedicament, and the step of the flowing fluid into an injection devicecomprises flowing combined fluid and medicament from the second vialinto an injection device under the force of pressurized gas.
 4. Themethod of claim 3 wherein the fluid is a diluent.
 5. The method of claim3 wherein the fluid is a first liquid medicament and the medicament inthe second vial is a second liquid medicament.
 6. The method of claim 3in which the medicament in the second vial is lyophilized, and thediluent reconstitutes the medicament.
 7. The method of claim 1 in whichthe injection device includes an expandable reservoir, and the fluid isflowed into the expandable reservoir under pressure from the pressurizedgas.
 8. The method of claim 7 in which the expandable reservoircomprises an elastomeric bladder.
 9. The method of claim 7 in which thereservoir is biased to expel the fluid or combined diluent andmedicament.
 10. The method of claim 1 in which pressurized gas is flowedfrom a pre-filled pressure vessel.
 11. The method of claim 10 in whichthe vessel includes a puncturable seal and the method includespuncturing the seal.
 12. The method of claim 1 in which the pressurizedgas is essentially pathogen free.
 13. The method of claim 1 includingfiltering the gas before it enters a vial.
 14. The method of claim 10 inwhich the pressure vessel is a gas-filled cartridge having a volume of10 ml or less.
 15. The method of claim 14 in which the cartridge hasvolume of about 1 ml or less.
 16. The method of claim 10 in which thepressure vessel initially contains gas at a pressure of greater thanabout 500 psig.
 17. The method of claim 1 in which the pressurized gasis an inert gas.
 18. The method of claim 1 in which the gas is selectedfrom the group consisting of nitrogen, helium, neon, argon, krypton, andxenon.
 19. The method of claim 7 including removing entrained gas fromthe fluid before it enters the expandable reservoir.
 20. The method ofclaim 1 in which the pressurized gas is flowed from a pre-filledcartridge having a volume of about 1 ml or less and a pressure of about900 psig or greater.
 21. The method of claim 1 including controlling theflow rate and/or pressure of the pressurized gas.